The final objective of this Phase II SBIR is to complete preclinical studies of a trivalent adenoviral vaccine against plague in preparation for human clinical trials. The plague vaccine project was selected in response to the growing concern surrounding the organism's possible use in a terrorism event. The NIAID and CDC, in response to this threat, has classified the organism as a Category A priority organism. Currently, there are no commercially available vaccines for protection against plague in the instance of a bioterrorism event. This concern is alarming, as multi-antibiotic-resistant strains of the plague bacterium, Y. pestis, exist in nature or have been engineered. Project Aims for this Phase II SBIR will focus on the production and evaluation of a vaccine candidate featuring the low calcium response (LcrV) antigen in combination with two other protective Y. pestis antigens, namely Caf1 (F1 capsular antigen) and YscF (a type 3 secretion system (T3SS) structural protein), in an adenoviral vector system. The project will test the hypothesis that a single, intranasal administration of the adenoviral vaccine can elicit a strong protective immune response in non-human primates (NHPs) against aerosol challenge with the fully virulent Y. pestis strain CO92. Project aims will also demonstrate the large-scale production capability of the vaccine necessary for meeting stockpiling or emergency scenarios. This program will provide a valuable first line of defense by deterrence for potential terrorists in search of weapons where no vaccine or treatment option exists. Further, the development of a multivalent adenoviral vaccine is not only significant for biodefense but also for combating global infectious disease. PUBLIC HEALTH RELEVANCE: The final objective of this Phase II SBIR is to complete preclinical studies of a trivalent adenoviral vaccine against plague in preparation for human clinical trials. Currently there is no licensed vaccine for human use to protect against infection with plague despite the pathogen's capability to inflict widespread morbidity and mortality upon exposure to both civilians and military personnel.